Conjugated Linoleic Acid: Cancer Fighter in Milk M.A. McGuire Department ofAnimal and Veterinary Science Uniµersity of Idaho, Moscow 83844-2330 Introduction lished40 concerning the effect of CLA on cancer used par­ tially purified extracts of CLA from grilled ground beef As an important source of nutrients, milk provides and demonstrated a reduction in the number of skin high-quality protein, energy, calcium and a variety of cancers, as well as the number of mice that had skin vitamins and minerals. Recent research has focused on cancers. Ip et al22 showed that dietary CLA is a potent altering the fat and protein content of milk and other inhibitor of mammary tumor development and growth dairy products in order to improve the nutrient content in rats (Figure 1). Further, Ip et al26 demonstrated that of these foods so that they more aptly reflect current CLA works as an anti-carcinogen regardless of dietary dietary recommendations and trends. For example, diet fat content or type of fat fed (corn oil vs lard). is a contributing factor to the onset or progression of Recent work demonstrated that CLA could inhibit some cancers, with epidemiological studies indicating the growth of human breast50 and prostate5 cancer cells diet composition may be related to 35 percent of human when implanted into immune-deficient mice. cancer deaths.11 A few substances in our diet have been Furthermore, consumption of CLA may play ben­ identified as anti-carcinogens, but most are of plant ori­ eficial roles in aspects of atherosclerosis, growth and dia­ gin and are only present in trace concentrations. How­ betes. First, Lee et al3 1 demonstrated that rabbits fed 0.5 ever, conjugated linoleic acid (CLA), a component of milk g CLA per day exhibited lower circulating LDL choles­ 0 fat, introduces an exciting twist to what we know about terol (the bad cholesterol) and triglyceride concentrations; "'O (D diet and cancer. Unlike most naturally occurring anti­ examination of the aortas showed less atherosclerosis. ~ carcinogens, CLA is potent at extremely low levels and Interestingly, recent epidemiological evidence14 shows no ~ (") (D present in foods from ruminant animals. increase in risk of coronary heart disease with greater 00 butter consumption, and intake of margarine (a food lack­ 00 0........ 00 Discussion ing CLA) actually has been associated with an increased ,-+- risk of heart disease. Thus, although more studies are '"i ~ 38 The National Academy of Sciences publication, needed, it may be possible that CLA is beneficial in pre­ ~...... Carcinogens and Anti-carcinogens in the Human Diet, vention of atherosclerosis in humans. 0p concluded " ... conjugated linoleic acid (CLA) is the only The second biological phenomenon, investigated fatty acid shown unequivocally to inhibit carcinogen­ more recently, concerns alterations in growth and body esis in experimental animals." Conjugated linoleic acid composition. During periods of catabolic stress caused refers to a series of positional and geometric isomers by endotoxin injections, chickens8 and mice37 lose less of linoleic acid with conjugated double bonds.16 These are fatty acids with 18 carbons and two double bonds 80 separated by one single bond. CLAs as a group are 70 important because they have been recognized as the only fatty acids shown unequivocally to inhibit carcino­ 60 38 ~ so genesis in experimental animals, and it is hearten­ Q E 40 ing to note that CLA is a potent anti-carcinogen in all ~ 22 =it 30 cancer models tested. ,44 While no intervention study in humans has exam­ 20 ined the role of CLA in cancer prevention or treatment, 10 epidemiologic evidence from Finland29 demonstrated a 0 protective effect of milk intake on the risk of breast can­ 0 0.0S 0.1 0.2S o.s cer in women, and milk is a major source of CLA in the % CLAindiet human diet.6 Beefis also an important source of CLA Figure 1. Response of mammary tumors in rats fed 6 25 in the human diet. In fact, the first examination pub- diets with varying levels of CLA (Ip et al ). SEPTEMBER, 2000 79 body weight when fed a diet containing CLA. These 11.30 The name "rumenic acid" was chosen because this observations suggest that CLA could alter tissue loss. CLA is present in the human diet primarily in foods Chin et al7 demonstrated that CLA may also affect tis­ (beef and dairy) derived from ruminant animals.6 While sue gain: rat pups nursing dams fed diets containing other CLAs can be found in foods for humans, rumenic CLA were larger than pups nursing dams fed diets with­ acid is the predominate form found naturally. Rumenic out CLA. While no consistent response in milk protein acid represents greater than 90% of the CLAs present content was observed, the CLA content of rat milk was in milk fat and over 75% of the CLAs present in beef enriched in the dams fed CLA. No data were presented fat.6 However, as mentioned previously, rumenic acid on the fat content of the milk. Further, Chin et al dem­ intake can now be increased by the ingestion of indus­ onstrated that postnatal weight gains increased 7% in trially-produced CLA supplements available from health rats fed CLA. On the other hand, Belury and Kempa­ food stores. Unfortunately, these supplements also pro­ Steczko1 noted slower growth rates in young adult mice vide other CLAs, as well as additional identified and fed CLA. Although body composition was not measured, unidentified fatty acids. lipid content ofliver increased with greater CLA intake. Very recent evidence suggests that CLA may, in fact, Should We Fortify Or Enrich Foods With alter body composition. Mice fed diets containing 0.5% Rumenic Acid? CLA exhibited nearly 60% less fat with an almost 10% increase in protein.41 Similar studies have demonstrated We have examined the presence ofCLAin human improved lean growth in growing pigs fed CLA-enriched milk and infant formula.36 Human milk contained more diets.39 In the very near future, pork could become a CLA than did all brands of infant formula tested and source of CLA in the human diet. over 80% was rumenic acid. Because of the potential The third area of biological effect is in control of for altered growth and body composition, it may be im­ diabetes. Feeding CLA to rats prone to developing dia­ portant to fortify infant formula with CLA. betes normalized glucose tolerance and improved For other ages, beef and dairy products are the pre­ hyperinsulinemia as effectively as current medications.20 dominate dietary sources of rumenic acid,46 with dairy However, the study was short-term and needs to be rep­ products the most substantial contributors (Figure 2). licated before the results can be applied to human health. Greater consumption of foods rich in rumenic acid 321 0 Nonetheless, if CLA can inhibit body fat accretion as increases circulating concentrations. · Further, lactat­ "'O (D demonstrated in mice, rats and pigs, then improvements ing women consuming large quantities of dairy products ~ in lean-to-fat ratios in the human body may be benefi­ and beef increased the concentration of rumenic acid in ~ 42 (") cial to diabetes-prone humans prone. This remains an their milk, again confirming the importance of rumenic (D 00 exciting area of research. acid intake in determining human rumenic acid status. 00 0........ However, the species of bacteria that make rumenic 00 ,-+- CLAs: Multiple Isomers, Multiple acid from linoleic acid can be found in the human co­ '"i ~ Biological Actions lon. 4 To test if circulating status of rumenic acid can be ~ 9 ...... altered by consumption of linoleic acid, Herbel et a/1 0 Many isomers of CLA are made during industrial fed subjects an oil and vinegar dressing for 6 weeks that p production, such as those utilized to produce CLA supple­ increased linoleic acid consumption 2.5-fold. At the end ments available in health food stores. These mixes of of the dietary intervention, no change in circulating con­ CLAs have been the testing material for cancer, athero­ centration of rumenic acid was detected on average, but sclerosis, growth and diabetes experiments. Is it pos­ it is noteworthy that a small number of subjects did re­ sible or probable that one isomer could cause such diverse spond to this intervention. This suggests that rumenic metabolic events as reduction in tumor development or acid needs to be present in the diet of most humans to growth, protection of arterial walls from plaque forma­ impact human rumenic acid status. tion, alterations in circulating lipoproteins and choles­ terol, promotion of lean growth while diminishing fat deposition, and regulation of milk fat synthesis? We be­ lieve it unlikely that one isomer is responsible for all bio­ □ Dairy logical activities and, thus; encourage further research ~Beef and discussion concerning CLAs and their biological im­ portance to focus on effects of each specific isomer. ■ Pork ■ Poultry What is Rumenic Acid? □ Other Rumenic acid is the term given to the CLA that possesses a double bond arrangement of cis-9 and ~rans- Figure 2. Sources ofrumenic acid in the human diet.46 80 THE BOVINE PROCEEDINGS-VOL. 33 The question is whether we, as animal scientists, Working out the pathways ofbiohydrogenation in should strive to increase the natural CLA content of beef the rumen using cultures of mixed and pure rumen bac­ and dairy products or simply focus on greater promo­ teria, rumen microbiologists have shown that rumenic tion of consumption of those currently available prod­ acid is the product of isomerization of linoleic acid (cis- ucts. From the Knekt et al29 study, it is clear that minor 9, cis-12 C18:2). 18 Many species ofbacteria can perform increases in consumption of milk (e.g.